Project Summary: Project 3, Neural Coding and Dynamics?Subcortical Regions Working memory, the ability to temporarily hold multiple pieces of information in mind for manipulation, is central to virtually all cognitive abilities. This multi-component research project aims to comprehensively dissect the neural circuit mechanisms of this ability across multiple brain areas. The individual parts of the project cohere conceptually, in part, because they all involve rodents trained to perform a type of decision-making task that is based on the gradual accumulation of sensory evidence and thus relies on working memory. Although most previous characterization of neural correlates of working memory and decision making has focused on cortical regions, there is growing appreciation that subcortical regions contribute to these processes as well. Thus, this project focuses on characterization of the neural dynamics underlying working memory and decision-making in a network of subcortical regions. Specifically, cellular-resolution two- and three-photon calcium imaging will be used to characterize neural coding and dynamics in dopamine neurons in the ventral tegmental area and substantial nigra, granule cells and Purkinje cells of the cerebellum, medium spiny neurons in the striatum, and pyramidal cells in the hippocampus. This data will be supplemented with multi-electrode recordings, which capture fast neural activity that calcium imaging cannot. The experiments will combine these two data types for the first time in the setting of a working memory and decision-making task. The results from this project, together with those from another component that investigates similar measures in neocortex, are expected to provide an unprecedented amount of data that will give new insight into the processing of task-relevant information during a cognitive task across a wide variety of cortical and subcortical areas. Another component will combine these results with temporally and spatially specific inactivation data from the other two components to build and constrain a biophysically realistic, multi-region computational model of the behavior.